Remission re-induction chemotherapy with clofarabine, topotecan, thiotepa, and vinorelbine for patients with relapsed or refractory leukemia Journal Article


Authors: Steinherz, P. G.; Shukla, N.; Kobos, R.; Steinherz, L.
Article Title: Remission re-induction chemotherapy with clofarabine, topotecan, thiotepa, and vinorelbine for patients with relapsed or refractory leukemia
Abstract: Background. We determined the maximum tolerated dose (MTD) of clofarabine when administered with topotecan, vinorelbine, thiotepa, and dexamethasone (TVTC) for children with relapsed or refractory acute leukemia, and observed the efficacy and toxicities of this therapy. Procedure. Twelve patients with acute lymphoblastic or myeloblastic leukemia were given a 14-day remission induction therapy. Clofarabine was administered at a dose of 30 or 40 mg/m2/day over 2 hr for five consecutive days in six patients each. Patients who achieved a remission proceeded to a stem cell transplant (HSCT). A second cycle could be administered prior to HSCT. Results. Of the six patients at the 30 mg/m 2 clofarabine dose, two achieved a complete response (CR) and one a PR and proceeded to BMT. Three patients had progressive disease. Five of the six patients at the 40 mg/m2 achieved a CR. Four proceeded to HSCT, and one relapsed prior to HSCT. One patient died on day 45 with marrow hypoplasia without evidence of leukemia. Hematologic and infectious adverse events were universal. The one dose limiting non-infectious toxicity observed was prolonged marrow hypoplasia. Conclusion. TVTC has significant anti-leukemic activity in both acute lymphoblastic and myeloblastic leukemia. The MTD of clofarabine is 40 mg/m2/day in this combination. This is the recommended dose for the phase II study in patients with refractory or relapsed leukemia, a population which has limited therapeutic options. © 2010 Wiley-Liss, Inc.
Keywords: adolescent; adult; cancer chemotherapy; child; clinical article; preschool child; school child; treatment response; child, preschool; antibiotic agent; acute granulocytic leukemia; leukemia, myeloid, acute; prednisone; disease course; neutropenia; salvage therapy; diarrhea; gastrointestinal hemorrhage; side effect; gemcitabine; chemotherapy; cytarabine; methotrexate; topotecan; drug megadose; antineoplastic agent; infection; liver toxicity; bone marrow suppression; etoposide; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; drug administration schedule; recurrence; cyclophosphamide; dexamethasone; vincristine; hematopoietic stem cell transplantation; antineoplastic activity; continuous infusion; pathology; cancer mortality; thiotepa; vinblastine; acute lymphoblastic leukemia; drug dose escalation; drug fever; febrile neutropenia; hypotension; cancer regression; acute leukemia; death; infant; mitoxantrone; daunorubicin; acute myeloblastic leukemia; drug derivative; remission; remission induction; single drug dose; asparaginase; recurrent disease; sepsis; precursor cell lymphoblastic leukemia-lymphoma; colitis; pancytopenia; drug toxicity; bacteremia; seizure; maximum tolerated dose; idarubicin; acute lymphocytic leukemia; drug administration; bloodstream infection; navelbine; leukemia relapse; lung infection; amylase blood level; triacylglycerol lipase blood level; granulocyte colony stimulating factor; meningitis; retreatment; clofarabine; tioguanine; heart arrest; cellulitis; adult respiratory distress syndrome; enterocolitis; refractory; aml; adenine nucleotides; arabinonucleosides; all; relapsed; guanine arabinoside; nelarabine; adenine nucleotide; arabinonucleoside; bone marrow hypoplasia; vein occlusion
Journal Title: Pediatric Blood and Cancer
Volume: 54
Issue: 5
ISSN: 1545-5009
Publisher: Wiley Periodicals, Inc  
Date Published: 2010-05-01
Start Page: 687
End Page: 693
Language: English
DOI: 10.1002/pbc.22321
PUBMED: 20205253
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: PBCEA" - "Source: Scopus"
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MSK Authors
  1. Peter G Steinherz
    179 Steinherz
  2. Rachel Kobos
    65 Kobos
  3. Neerav Shukla
    83 Shukla